Table 1.

Summary of epidemiological and clinical findings supporting the gateway hypothesis. Surveys of adolescents and/or young adults were conducted to assess gateway effects of nicotine on subsequent drug use. Details of these selected epidemiological and clinical surveys and findings are highlighted, including age, data source, data analysis, and main observation(s).

Age	Data source and analysis	Main observation(s)	Reference(s)
24–25 years (follow-up of former adolescents aged 15–16 years)	Longitudinal cohort of former New York State high school students, followed from grades 10 and 11 (ages 15.7–34.2). Detailed monthly drug use histories were obtained. The following sequence of progression was tested: alcohol, cigarettes, marijuana, other illicit drugs, and prescribed psychoactive drugs. In addition, months of use and non-use of cigarettes and cocaine were identified.	Sequence pattern: Cigarettes preceded marijuana use with or without initial alcohol use among women. However, in men, alcohol consistently preceded marijuana use even in the absence of initial cigarette use. Cigarettes preceded other illicit drugs among women, but not among men. Cigarette and cocaine use: Most cocaine users smoked cigarettes before they started using cocaine. In addition, most cocaine users started using cocaine while they were actively smoking cigarettes (i.e., within the same month).	3,5
11–16 years	Subjects were sampled from eight public schools in Milwaukee, Wisconsin. The subjects were interviewed twice, first during 1979–80 and again during 1981–82. Eighty-nine percent of those interviewed initially were re-interviewed two years later.	Cigarette use fell on a cumulative (Guttman) scale of use with other drugs (e.g., marijuana, beer, liquor, stimulants, depressants). Having tried substances lower on the Guttman scale made one significantly more likely to be using substances higher on the scale two years later. Use of cigarettes during middle or early high school significantly increased the likelihood that the subject would be using other drugs (e.g., beer, marijuana) two years later.	4
Years 12–15, 16–17, 18–25, 26–34, 35–49, 50 or over	1994 National Household Survey on Drug Abuse. Data were analyzed to clarify whether cigarette smoking has any effect on the initiation of illegal drug use.	Individuals who had smoked cigarettes were far more likely to use marijuana, cocaine, heroin, and/or crack. Those who smoked cigarettes before age 15 were up to 80 times more likely to use illegal drugs than those who did not. Cocaine was the drug most likely to be used among young cigarette smokers.	5
16–34 years	National Epidemiological Study of Alcohol Related Consequences, a cohort representative of the U.S. population. The rates of lifetime cocaine dependence were compared among three groups: 1) those who had started to use cocaine after they had started to smoke and before they had stopped smoking, 2) those who had started cocaine use before beginning to smoke; and 3) those who had ever smoked 0–100 cigarettes.	The rate of cocaine dependence was the highest among cocaine users who initiated cocaine after having smoked cigarettes. The rates of dependence were much lower among those who initiated cocaine before smoking or who had ever smoked 0–100 cigarettes.	8
11–20 years	National Longitudinal Study of Adolescent to Adult health data spanning a 14-year period. The relationship between gateway drugs during 11–20 years of age and drug use in adulthood was analyzed using generalized estimating equation regression models.	Exposure to marijuana and illegal substances during young adulthood was positively associated with illegal substance and cocaine use. Interactions between the gateway drugs and reporting high depressive symptoms in adolescence or adulthood were associated with increased use of marijuana, illegal drugs, and cocaine in early or young adulthood.	14
14–30 years	Systematic review and meta-analysis of longitudinal studies that assessed initial use of e-cigarettes and subsequent cigarette smoking. Study selection: longitudinal studies reporting odds ratios for cigarette smoking initiation associated with ever use of e-cigarettes or past 30-day cigarette smoking associated with past 30-day e-cigarette use.	E-cigarette use was associated with greater risk for subsequent initiation of cigarette smoking and past 30-day cigarette smoking.	17
14–16 years	Subjects were sampled from 10 public schools in Los Angeles, California. Students completed surveys at baseline (grade 9) and at a 24-month follow-up (grade 11). Associations of baseline e-cigarette, hookah, or combustible cigarette use with ever marijuana use (initiation), current marijuana use (past 30 days), and current dual use of marijuana and tobacco products were examined at the 24-month follow-up.	High schoolers who used e-cigarettes or hookah at baseline compared with those who did not were more likely to report initiation and current use of marijuana as well as dual use of tobacco and marijuana. E-cigarette and hookah use at age 14 years was associated with a 3.6- to 4-fold increase in the odds of initiating and currently using marijuana two years later. The use of e-cigarettes, hookah, and combustible cigarettes in early adolescence more than doubled the odds of currently using both tobacco and marijuana by mid-adolescence.	19